One hundred ninety-two African Americans have participated. This cohort is known as TARA for: Triglyceride and Cardiovascular Risk in African-Americans. In addition 160 Black Africans (who have immigrated to the United States have enrolled. This cohort is known as BART for: Black Africans and Cardiovascular Risk from Triglyceride. The sample of African-Americans participating can be considered representative of the African-American population of the United States because the prevalence of obesity (43%), pre-diabetes (22%) and hypertension (21%) is similar to NHANES data. NHANES stands for National Health and Nutrition Examination and is a nationwide survey with thousands of participants. However, there is no national data on the metabolic and diabetic health of Black Africans living in the United States. To explore risk for diabetes, we are relying not just on fasting glucose but are also performing oral glucose tolerance tests and measuring A1C levels. In performing these tests, we have made the observation that the overall rate of pre-diabetes and hypertension is almost twice as high in African men than African-American men. Furthermore, the rate of undiagnosed diabetes in self-identified healthy individuals was 3% in Africans vs 0% in African American men. In contrast the rate of hypertension, diabetes and pre-diabetes are similar in African women and African American women. Identifying the reasons for this less healthy metabolic profile of African men compared to African-American men has become a major focus of research in this protocol. To improve and then maintain good health in African men, it is essential to understand why pre-diabetes, diabetes and hypertension is occurring in African men even though African men are less obese, more likely to be non-smokers, more likely to be married and have similar educational levels and income as African-American men. The body size of both the African-American and African participants range from lean to obese. The mean body mass index of participants is 30.6 kg/m2 for African Americans but only 26.4 kg/m2 in BA-USA. Body mass index is a mathematical method used to correct weight for height. Due to the broad range of body mass index in the participants it is possible to make conclusions about the relationship of body size to insulin resistance. It is insulin resistance that is a major factor in the development of diabetes, heart disease and hypertension. To have a reliable way to predict insulin resistance based on body size is essential. A key way to assess body size is by waist circumference as waist circumference is a measure of central obesity. We have found in African American men that a waist circumference of 102 cm in men predicts both insulin resistance and obesity. This is in agreement with the National Cholesterol Education Program values for whites. However, in African American women we found that a waist circumference of 98 cm predicted both insulin resistance and obesity. Based on investigations in white women the National Cholesterol Education Program recommends that a waist circumference threshold of 88 cm be used. Therefore our work demonstrates the need for ethnic-specific modifications of guidelines in women. In addition, we have now expanded our study of total and central obesity to include both African American women as well as African women. Plus we are in the process of comparing and combining our results with investigators from South Africa and through a collaboration with Dr. Rotimi (NHGRI) with West African women living in Nigeria and Ghana. Very importantly, we have found that the relationship of waist circumference to body mass index is similar in African-American women, African women living in the US, West African women living in Nigeria and Ghana and Black South African women. Therefore when the waist circumference which predicts insulin resistance in African-American women, our results suggest that the same waist circumference is likely to be effective in African women. Elevated TG and low HDL are considered lipid hallmarks of insulin resistance. However while elevated TG is a marker of insulin resistance in whites, we have shown that TG is not a marker of insulin resistance in African Americans. The investigation of the relationship of TG to insulin resistance is such an important component of this research program, that the cohort of African-Americans participating in this protocol are known as TARA which stands for Triglyceride and Cardiovascular Risk in African Americans. Results from TARA were so impressive that the hypothesis that TG was not a marker of insulin resistance in African Americans was subsequently tested in NHANES data collected from 1999-2001. In this NHANES data set of whites, African-Americans and Mexican Americans, the fact that TG was not a marker of insulin resistance was confirmed. However, TG was a powerful marker of insulin resistance in whites and Mexican Americans. Altogether this research on race differences in the relationship of TG to insulin resistance demonstrates the need to develop for ethnic-specific guidelines. More recently the TG/HDL ratio at a level of >3.0 has been suggested to be a marker of insulin resistance. This is well established in whites. But we have shown using TARA data that this did not work in African Americans. Very recently, we were asked to prove if this was the case using the much larger data set of the Jackson Heart Study, a cohort of 2000 African Americans living in Jackson, Mississippi. This larger dataset was a sufficient size to examine men and women separately. We found, that the ratio at the ethnic-specific level of 2.5 actually worked in African-American men to predict insulin resistance, but did not work in African-American women. In fact, in women the ratio would give incorrect results >50% of the time. Therefore to identify and prevent diseases related to insulin resistance in African American women, we have to identify which tests do work. Best health will only be achieved with accurate and correct early screening. Having found that the TG/HDL ratio was not effective predictor of insulin resistance in African-American women, we tested the ratio in white South African women, Black South African women, West African women from Ghana and Nigeria and African-American women. We found that while the ratio effectively predicted insulin resistance in the white women, it did not work in any group of women of African descent. Again demonstrating that findings related to insulin resistance which initially was determined in African-American women applied to African women. Another key component of this program is the development of an index of free fatty acid sensitivity to insulin. Free fatty acids are the building blocks used by the body to build TG. There are 3 fatty acids in each TG particle. In this initiative we are working with mathematicians. The modeling is underway. Due to the multiplicity of hormones that affect free fatty acid levels as well as the wide range of biological variation in free fatty acids, achieving a model of the effect of insulin on free fatty acids is a great challenge. Our preliminary findings are that the rate of clearance of free fatty acids from the circulation is related to insulin concentration rather than insuli resistance. If confirmed this will represent a paradigm change. We currently believe that free fatty acid clearance, high peripheral fat, obesity and low normal TG may be linked by high insulin concentrations. If this is confirmed in future studies we would have made a big step forward in understanding both race and ethnic differences in TG metabolism as well. In summary, we are dedicated to preventing cardiovascular disease and diabetes in people of African descent worldwide by achieving a better understanding the ethnic-specific risk factors.